title: 5-HT1A-receptor agonist modified amygdala activity and amygdala-associated social behavior in a valproate-induced rat autism model.
abstract: Accumulating evidence suggests that dysfunction of the amygdala is related to abnormal fear processing, anxiety, and social behaviors noted in autistic spectrum disorders (ASDs). In addition, studies have shown that disrupted brain serotonin homeostasis is linked to ASD. With a valproate (VPA)-induced rat ASD model, we investigated the possible role of amygdala serotonin homeostasis in autistic phenotypes and further explored the underlying mechanism. We first discovered that the distribution of tryptophan hydroxylase immunoreactivity in the caudal raphe system was modulated on postnatal day (PD) 28 of the VPA-exposed offspring. Then, we found a significantly higher serotonin transporter availability in the amygdala of the VPA-exposed offspring on PD 56 by using single photon emission computed tomography and computed tomography co-registration following injection of (123)I-labeled 2-((2-(dimethylamino)methyl)phenyl)thio)-5-iodophenylamine((123)I[ADAM]). Furthermore, treatment with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, increased social interaction and improved fear memory extinction in the VPA-exposed offspring. 8-OH-DPAT treatment also reversed the characteristics of miniature excitatory post-synaptic currents as well as paired pulse facilitation observed in lateral amygdala slices. These results provided further evidence to support the role of the amygdala in characteristic behavioral changes in the rat ASD model. The serotonergic projections that modulate the amygdala function might play a certain role in the development and treatment of behavioral symptoms exhibited in individuals with ASD.
authors.affiliation: Department of Anatomy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chao-Chuan
authors.initials: CC
authors.lastname: Wang
authors.forename: Hui-Ching
authors.initials: HC
authors.lastname: Lin
authors.forename: Yun-Han
authors.initials: YH
authors.lastname: Chan
authors.forename: Po-Wu
authors.initials: PW
authors.lastname: Gean
authors.forename: Yen Kung
authors.initials: YK
authors.lastname: Yang
authors.forename: Po See
authors.initials: PS
authors.lastname: Chen
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000679:Amygdala / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001321:Autistic Disorder / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D002928:Cinanserin / Q000031:analogs & derivatives; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials; D005108:Extinction, Psychological / Q000187:drug effects; D005239:Fear / Q000187:drug effects; D005260:Female; D008297:Male; D008568:Memory / Q000187:drug effects; D055369:Miniature Postsynaptic Potentials; D064847:Multimodal Imaging / Q000379:methods; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects* / Q000378:metabolism; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D012919:Social Behavior; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D014635:Valproic Acid
chemical_list: C413491:2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine; D019275:Radiopharmaceuticals; D058825:Serotonin 5-HT1 Receptor Agonists; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D044282:Receptor, Serotonin, 5-HT1A; D014635:Valproic Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D014365:Tryptophan Hydroxylase; D002928:Cinanserin